Increased feeding in response to decreased glucose utilization in the rat and monkey.

SMITH, GERARD P., AND ALAN N. EPSTEIN. Increased feeding in response to decreased glucose utili<ation ilz the rat and monkey. Am. J Physiol. 217(4) : 1083-1087. 1969.-The glucostatic hypothesis for the control of food intake predicts that decreased glucose utilization leads to increased food intake. Since the glucose analogue, 2-deoxy-D-glucose (Z-DG), produces decreased intracellular glucose utilization of most tissues and particularly of brain, the injection of 2-DG into 5 monkeys and 28 rats provided an explicit test of the predicted relationship. Both monkeys and rats ate more after 2-DG. The most effective systemic doses of Z-DG were 300 mg/kg (iv) in monkeys and 750 mg/kg (ip) in rats. Larger doses ( < 1,000 mg/kg) produced drowsiness, stupor, ataxia, or retching, but not convulsions. When separate groups of rats were tested with either insulin (6 U Iletin) or 2-DG (750 mg/kg), they increased their mean food intake to approximately the same amount, but the rats treated with Z-DG ate sooner. Shorter latency of feeding with 2-DG is interpreted as resulting from the fact that 2-DG produces decreased glucose utilization of brain directly, whereas insulin reduces cerebral glucose utilization indirectly as a consequence of hypoglycemia. Since Z-DG produced marked hyperglycemia during the period of increased feeding, these results show that the abrupt onset of decreased glucose utilization, not hypoglycemia, is a sufficient condition for feeding in mammals.